Critical amino-terminal segments in insertion of rat liver cytochrome P450 3A1 into the endoplasmic reticulum membrane

Broek, Peter J.A. Van den; Barroso, Margarida; Lechner, Maria Celeste

doi:10.1007/bf01938869

Cited by 11 publications

(2 citation statements)

References 27 publications

(23 reference statements)

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“…The CYP3A subfamily includes five rat (5), six mouse (6)(7)(8)(9), and four human genes (10)(11)(12)(13) along with many more in other species. Apart from liver, extrahepatic CYP3A expression is observed in intestine, leukocytes, and brain (14).…”

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confidence: 99%

Genomic characterization and regulation of CYP3a13: role of xenobiotics and nuclear receptors

et al. 2003

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We report that CYP3a13 gene, located on mouse chromosome 5, spans 27.5 Kb and contains 13 exons. The transcription start site is 35 bp upstream of the coding region and results in a 109 bp 5' untranslated region. CYP3a13 promoter shows putative binding sites for retinoid X receptor, pregnane X receptor, and estrogen receptor. CYP3a13 shows a broad tissue distribution with predominant expression in liver. Although CYP3a13 shares 92% nucleotide identity with the female-specific rat CYP3A9, its expression does not exhibit sexual dimorphism. Ligand activation of peroxisomal proliferator-activated receptor-gamma and retinoid X receptor inhibit expression of CYP3a13 at the transcription level in a tissue-specific manner. Another novel finding is hepatic induction of CYP3a13 by dexamethasone occurring only in pregnane X receptor null mice. We also report that pregnane X receptor is essential to maintain robust in vivo basal levels of CYP3a13 in contrast to CYP3a11. CYP3a13 protein expressed in vitro can metabolize clinically active drugs ethylmorphine and erythromycin, as well as benzphetamine. We conclude that CYP3a13 is regulated differentially by various nuclear receptors. In humans this may lead to altered drug metabolism, as many of the newly synthesized ligands/drugs targeted toward these nuclear receptors could influence CYP3A gene expression.

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Genomic characterization and regulation of CYP3a13: role of xenobiotics and nuclear receptors

et al. 2003

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“…The N‐terminus of LdSHD consists a hydrophobic sequence and a proline‐glycine rich domain (Fig. ), a typical character of microsomal CYPs (Van den Broek et al ., ). Moreover, LdSHD has two positively charged residues near the heme‐binding domain, a typical feature of mitochondrial enzymes (Werck‐Reichhart & Feyereisen, ) (Fig.…”

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confidence: 97%

The P450 enzyme Shade mediates the hydroxylation of ecdysone to 20‐hydroxyecdysone in the Colorado potato beetle, Leptinotarsa decemlineata

Kong

et al. 2014

Insect Molecular Biology

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Ecdysone 20-monooxygenase (E20MO), a cytochrome P450 monooxygenase (CYP314A1), catalyses the conversion of ecdysone (E) to 20hydroxyecdysone (20E). We report here the cloning and characterization of the Halloween gene Shade (Shd) encoding E20MO in the Colorado potato beetle, Leptinotarsa decemlineata. LdSHD has five conserved motifs typical of insect P450s, ie the Helix-C, Helix-I, Helix-K, PxxFxPE/DRF (PERF) and heme-binding motifs. LdShd was expressed in developing eggs, the first to fourth instars, wandering larvae, pupae and adults, with statistically significant fluctuations. Its mRNA was ubiquitously distributed in the head, thorax and abdomen. The recombinant LdSHD protein expressed in Spodoptera frugiperda 9 (Sf9) cells catalysed the conversion of E to 20E. Dietary introduction of double-stranded RNA (dsRNA) of LdShd into the second instar larvae successfully knocked down the LdShd expression level, decreased the mRNA level of the ecdysone receptor (LdEcR) gene, caused larval lethality, delayed development and affected pupation. Moreover, ingestion of LdShd-dsRNA by the fourth instars also down-regulated LdShd and LdEcR expression, reduced the 20E titre, and negatively influenced pupation. Introduction of 20E and a nonsteroidal ecdysteroid agonist halofenozide into the LdShd-dsRNA-ingested second instars, and of halofenozide into the LdShd-dsRNA-ingested fourth instars almost completely relieved the negative effects on larval performance. Thus, LdSHD functions to regulate metamorphotic processes by converting E to 20E in a coleopteran insect species Le. decemlineata.

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KNOCKDOWN OF CS‐SPOOK INDUCES DELAYED LARVAL MOLTING IN RICE STRIPED STEM BORER Chilo suppressalis

Shahzad

Yao

et al. 2014

Arch Insect Biochem Physiol

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Spook has essential roles in the biogenesis of the molting hormone 20-hydroxyecdysone (20-E). The function of spook in the rice striped stem borer (SSB) Chilo suppressalis remains unclear, prompting our hypothesis that it exerts actions similar to those reported for other insect species. Here we amplified the full-length transcript of spook (Cs-Spook) in SSB by 5' and 3' rapid amplification of cDNA ends. Cs-Spook has conserved P450 motifs such as Helix-C, Helix-I, Helix-K, and PERF motif (PxxFxPxRF). It was highly expressed in late instar larvae but less so in newly molted larvae. Cs-Spook was highly expressed in prothoracic glands. Cs-Spook was knocked down by dsRNA treatments. Compared with controls, the gene expression level was reduced to 9% at 24 h post injection (PI), 33% at 48 h PI, and 24% at 72 h PI. The ecdysteroid titer decreased significantly in the dsRNA-treated group (P < 0.05), resulting in delayed larval development. The delayed development in dsRNA-treatment group was rescued by treating with 20-E. Our work demonstrates that Cs-Spook participates in the biogenesis of 20-E and regulates the molt of SSB, as seen in other species.

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Critical amino-terminal segments in insertion of rat liver cytochrome P450 3A1 into the endoplasmic reticulum membrane

Cited by 11 publications

References 27 publications

Genomic characterization and regulation of CYP3a13: role of xenobiotics and nuclear receptors

Genomic characterization and regulation of CYP3a13: role of xenobiotics and nuclear receptors

The P450 enzyme Shade mediates the hydroxylation of ecdysone to 20‐hydroxyecdysone in the Colorado potato beetle, Leptinotarsa decemlineata

KNOCKDOWN OF CS‐SPOOK INDUCES DELAYED LARVAL MOLTING IN RICE STRIPED STEM BORER Chilo suppressalis

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